Aziridines, the smallest nitrogen heterocyclic compounds, exhibit numerous important applications, including serving as essential motifs of biologically interesting compounds and as valuable synthons for preparation of various amine derivatives. See, for example, Hu, Tetrahedron 2004, 60, 2701; Sweeney, Chem. Soc. Rev. 2002, 31, 247; Zwanenburg et al., Top. Curr. Chem. 2001, 216, 93; and McCoull et al., Synthesis 2000, 1347. Among several approaches, metal-catalyzed asymmetric aziridination of alkenes with proper nitrene sources represents one of the most general and direct methods for construction of the three-membered ring structure. See, for example, Muller et al., Chem. Rev. 2003, 103, 2905; Jacobsen, In Comprehensive Asymmetric Catalysis; Jacobsen et al., Eds.; Springer: Berlin, 1999, 2, 607; and Halfen, Curr. Org. Chem. 2005, 9, 657.
Despite the successful development of catalytic epoxidation from alkenes over the last 30 years, the nitrogen analogue, catalytic aziridination, has languished behind. Part of the reason is the lack of nitrogenous variants of peroxides or dioxygen, which are used to form epoxides in conjunction with alkenes. Today, “C2+N1” aziridination reactions that combine an alkene and a nitrene fragment typically use iodoimine reagents such as PhI═NTs (Ts=tosylate), chloramine-T, or tosyl azide as the nitrene reagent. The disadvantage of these reactions is that the tosyl group must be removed before the desired final substituent can be placed on the ring, which reduces the atom economy and can lead to ring degradation. Organic azides are an alternative to these current nitrene reagents. Aryl azides can be easily synthesized in one step from amines and are tolerant of a wide variety of functional groups. Finally, since the correct functionality can be installed on the organic azide prior to catalysis, the use of organic azides instead of PhI═NTs should improve the atom economy of these reactions, thereby eliminating the step of removing the tosylate group before installing the desired moiety on the nitrogen atom.
A catalytic “C2+N1” aziridination that is successful with a wide variety of substrates, both for alkenes and organic azides, would be a significant advance in chemical synthesis. A very limited number of catalytic ruthenium, cobalt, and iron porphyrin systems have been developed that perform “C2+N1” aziridination with organic azides, but they are limited to strongly electron-withdrawing aryl azides (such as p-nitrophenyl azide) and/or styrene derivatives for the alkene. Thus, the need exists for a new class of aziridination catalysts that do not suffer from the above identified deficiencies. Since the aziridine functional group is found in natural products and also used in pharmaceuticals, broadening the scope of the aziridination reaction is significant.